Clinical Activity, Toxicity, Biomarkers, and Future Development of CTLA-4 Checkpoint Antagonists

Seminars in Oncology
Margaret K Callahan, Jedd D Wolchok

Abstract

Evidence that the immune system can recognize, and in some cases control or even eliminate tumors, is increasingly clear. Encouraging T-cell activation by blocking regulatory or "checkpoint" molecules is a potent way to amplify anti-tumor immune responses. Successfully exploiting this concept, a new class of anti-cancer therapies, "checkpoint-blocking" antibodies has emerged. The first checkpoint-blocking antibody to enter the clinic was ipilimumab, an antibody that blocks the co-inhibitory receptor cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Herein we review the clinical development of CTLA-4 blocking antibodies, including preclinical studies, clinical activity, toxicities, the search for potential biomarkers, and early clinical experience with combinations.

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Citations

Mar 13, 2016·Seminars in Oncology·Malgorzata E WojtowiczAsad Umar
May 6, 2016·Frontiers in Immunology·Nicholas A Cacalano
May 7, 2016·Genes & Development·Philippe Gascard, Thea D Tlsty
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Sep 7, 2017·Current Medicinal Chemistry·Weiqiang ZhouGuangdi Wang

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